Tag Archives: hepatotoxicity

Activity of the mitochondrial isoenzymes of endogenous aldehydes catabolism under the conditions of acetaminophen-induced hepatitis

O. M. Voloshchuk, G. P. Kopylchuk, Y. I. Mishyna

Yuriy Fedkovych Chernivtsi National University, Institute of Biology, Chemistry and Natural Resources, Ukraine;
e-mail: o.voloschuk@chnu.edu.ua

The research deals with the determination of the activity of aldehyde dehydrogenase (EC 1.2.1.3), aldehyde reductase (EC 1.1.1.21) as well as the content of TBA reactive substances and protein carbonyl derivates in the rat liver  cytosolic fraction under the conditions of acetaminophen-induced hepatitis and protein deficiency. The most pronounced decrease in the activity of enzymes utilizing endogenous aldehydes is observed in the liver cytosolic fraction of animals with toxic liver injury maintained under the conditions of alimentary protein deficiency. Meanwhile, the accumulation of TBA reactive substances and protein carbonyl-derivates in the liver cytosolic fraction of animals of this experimental group was established. The accumulation of aldehyde products of lipid and protein oxidative damage on the background of the reduction in the activity of enzymes providing aldehyde catabolism may be considered as a possible mechanism underlying hepatocyte dysfunction under the conditions of toxic damage in protein-deficient animals.

Hepatotoxicity of bisphenol A under conditions of differential supplementation with retinoids

I. O. Shmarakov, V. L. Borschovetska, L. P. Ivanishchuk, M. M. Marchenko

Yuriy Fed’kovych Chernivtsi National University, Ukraine;
e-mail: igor.shmarakov@gmail.com

Classical xenoestrogenic in vivo effects of bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) are well-described in the literature, however the molecular mechanisms of BPA-induced hepatotoxicity are not fully characterized. The work is aimed to assess biochemical markers of BPA induced hepatotoxicity under conditions of differential supplementation with retinoids. We demonstrate that the absence of hepatic retinyl esters as the main form of vitamin A storage provides for a resistance to BPA induced liver damage. Retinoid supplementation increases the hepatotoxic effects of bisphenol A, evidenced in higher indexes of oxidative damage of lipids, proteins and non-protein thiol groups as well as increase of serum alanine  aminotransferase activity and myeloperoxidase activity in liver parenchyma. The absence of hepatotoxicity signs when hepatic retinoid stores are depleted and their presence during normal or excessive retinoid supplementation suggest that hepatic retinoid availability is one of the factors determining the hepatotoxicity of bisphenol A.

Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma

E. A. Gudz1, N. M. Hula1, T. N. Goridko1, Y. M. Bashta1,
A. I. Voyeikov1, A. G. Berdyshev1, H. V. Kosiakova2,
R. R. Panchuk3, R. S. Stoika2, A. A. Ryabtseva3, O. S. Zaichenko3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua;
2Institute Biology of Cell, National Academy of Sciences of Ukraine, Lviv;
3National University “Lvov Politekhnika”, Ukraine

The aim of the study was to evaluate the possibility to reduce the doxorubicin toxic effects by its immobilization with N-stearoylethanolamine (NSE) on nanocarier polyethylene glycol. The studied  parameters of the doxorubicin toxicity were: the level of creatinine in the mice blood plasma and activity of alanine aminotransferase and aspartate aminotransferase in the blood plasma of mice. The activity of catalase superoxide dismutase, glutathione peroxidase and intensity of lipid peroxidation was determined in the tissues of the heart, kidneys and liver. Doxorubicin in the content of nanocarrier alone caused an increase of serum creatinine and aspartateaminotrasferase activity in plasma of experimental animals with carcinoma. Nanocomposite which contained doxorubicin and NSE, did not cause an increase of these parameters. It has been shown that the administration of a carrier containing doxorubicin to mice with Lewis lung carcinoma caused the decrease of  catalase  activity in mice with carcinoma. The combination of NSE and doxorubicin on the carrier led to the normalization of this parameter to the level of intact animals. NSE immobilized on a carrier together with doxorubicin caused a decrease in the activity of superoxide dismutase in the kidney tissue of mice with tumor. The tumor growth caused the increase of the of superoxide dismutase in mice. The administration of a carrier which contained doxorubicin and NSE normalized superoxide dismutase in heart tissue contrary of kidney. The obtained results show the antitoxic and antioxidant effects of N-stearoylethanolamine immobilized in the nanocarrier complex together with doxorubicin.

Mechanism of hepatoprotective action of methionine and composition “Metovitan” against a background of antituberculosis drugs administration to rats

S. I. Anisimova1, G. V. Donchenko2, Yu. M. Parkhomenko2, V. M. Kovalenko1

1SI Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kovalenko_toxy@yahoo.com

Oral administration of antituberculosis drugs to rats for 60 days in doses that are equivalent to clinical ones, causes changes in mRNA levels expression of liver cytochrome P-450 isoforms CYP3A2, CYP2C23, CYP2E1 and pro- and antioxidant state. Experimental composition “Metovitan” given with anti-TB drugs provided a correction of these abnormalities, that is evidenced by modulation of the level of CYP3A2, CYP2C23, CYP2E1 gene expression and antioxidant activity, inhibition of lipid peroxidation. “Metovitan” normalizes the enzymatic activity and content of total billirubin in the blood serum, shows high hepatoprotective properties, exceeding the efficiency of methionine.

Organ-specific antitoxic effects of N-stearoilethanolamine male mice with lewis carcinoma under indoxorubicin intoxication

E. A. Goudz, N. M. Gulа, T. N. Goridko, Y. N. Bashta, A. I. Voyeikov

Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua

With the introduction of doxorubicin into mice with Lewis carcinoma in the heart and liver tissues and kidney the organ-antitoxic effects of N-stearoilethanolamine (NSE) were found, which depended on its concentration. Administration of doxorubicin to male mice leads to an increase in the level of urea and creatinine, as well as activation of ALT in blood plasma. Introduction of NSE resulted in normalization of these parameters to the level of intact animals. In the heart tissue  doxorubicin has multi-directional effects on the activity of antioxidant enzymes, in particular it decreases the activity of catalase and superoxide dismutase activity increases. Introduction of NSE normalizes these two indicators. It was found that tumor growth leads to an increase in the activity of glutathione peroxidase and superoxide dismutase. Introduction of NSE normalizes activity of these enzymes. Doxorubicin causes an increase in catalase activity in the kidney of mice with tumour, NSE prevented the increase in the activity of the above enzyme. The cancer process leads to increased levels of catalase activity in the liver of tumour-bearing mice, the introduction of NSE decreases the enzyme activity.

Hepatoprotective activity of exogenous RNA

 I. O. Shmarakov1, Т. V. Marchyshak1, V. L. Borschovetska1,
M. M. Marchenko1, Z. Yu. Tkachuk2

1Yuriy Fedkovych Chernivtsi National University, Ukraine;
е-mail: igor.shmarakov@gmail.com;
2Institute of Molecular Biology and Genetics,
National Academy of Sciences of Ukraine, Kyiv;
е-mail: ztkachuk@yahoo.com

Hepatoprotective activity of Nuclex, a pharmaceutical composed of low-molecular yeast RNA, was investigated during acute and chronic thioacetamide-induced hepatotoxicity. It is demonstrated, that Nuclex administration at a dose of 200 mg/kg during acute and chronic liver injury produces hepatoprotective effect, which is associated with decrease in liver parenchyma lesions and in its inflammatory infiltration. Nuclex application attenuates thioacetamide-induced free radical damage of hepatic biopolymers, expressed in the reduction of TBA-reactive products, carbonyl derivatives, and recovery of protein thiol groups and reduced glutathione levels.

Biochemical indicators of hepatotoxicity in blood serum of rats under the effect of novel 4-thiazolidinone derivatives and doxorubicin and their complexes with polyethyleneglycol-containing nanoscale polymeric carrier

L. I. Kоbylinska1, D. Ya. Havrylyuk1, А. О. Ryabtseva2, N. E. Mitina2,
О. S. Zаichenko2, R. B. Lesyk1, B. S. Zіmenkovsky1, R. S. Stoika3

1Danylo Halytsky Lviv National Medical University, Ukraine;
e-mail: lesya8@gmail.com;
2Lviv Polytechnic National University, Ukraine;
3Іnstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv

The aim of this study was to compare the effect of new synthetic 4-tiazolidinone derivatives (compounds 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethyleneglycol-containing nanoscale polymeric carrier on the biochemical indicators of hepatotoxicity in blood serum of rats. The activity of enzymes considered as the markers of hepatotoxicity, as well as the concentration of total protein, urea and creatinine were measured in blood serum of rats. It was found that after injection of investigated compounds the activities of alanine aminotransferase, alkaline phosphatase and α-amylase increased in comparison to control. Doxorubicin injection was accompanied by 4-fold increase in the activity of γ-glutamyltransferase, and injection of compound 3833 led to 2.5-fold elevation of the activity of this enzyme. Complexation of these аntineoplastic derivatives with a synthetic nanocarrier lowered the activity of the investigated enzymes substantially if compared to the effect of these compounds in free form. The most evident decrease was measured for α-amylase, γ-glutamyltransferase and lactate dehydrogenase activities. The normalization of concentrations of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with a polymeric carrier comparing with their introduction in free form was also detected. Thus, the immobilization by novel polymeric carrier of anticancer drugs possessing high general toxicity in the treated organism mitigates their toxic effect, which is evident as normalization of specific biochemical indicators of the hepatodestructive effects of the anticancer drugs.